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PML targeting eradicates quiescent leukaemia-initiating cells

机译:以PML为靶标可消除静止期白血病引发细胞

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摘要

The existence of a small population of 'cancer-initiating cells' responsible for tumour maintenance has been firmly demonstrated in leukaemia. This concept is currently being tested in solid tumours. Leukaemia-initiating cells, particularly those that are in a quiescent state, are thought to be resistant to chemotherapy and targeted therapies, resulting in disease relapse. Chronic myeloid leukaemia is a paradigmatic haematopoietic stem cell disease in which the leukaemia-initiating-cell pool is not eradicated by current therapy, leading to disease relapse on drug discontinuation. Here we define the critical role of the promyelocytic leukaemia protein (PML) tumour suppressor in haematopoietic stem cell maintenance, and present a new therapeutic approach for targeting quiescent leukaemia-initiating cells and possibly cancer-initiating cells by pharmacological inhibition of PML.
机译:在白血病中已明确证明存在少量负责肿瘤维持的“癌起始细胞”。该概念目前正在实体瘤中进行测试。白血病引发细胞,特别是处于静止状态的细胞,被认为对化学疗法和靶向疗法有抗性,导致疾病复发。慢性粒细胞白血病是一种典型的造血干细胞疾病,其中目前的疗法并未消除白血病的起始细胞库,导致药物停用后疾病复发。在这里,我们定义了早幼粒细胞白血病蛋白(PML)肿瘤抑制因子在造血干细胞维持中的关键作用,并提出了通过药理学抑制PML靶向静止性白血病起始细胞和可能的癌症起始细胞的新治疗方法。

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  • 来源
    《Nature》 |2008年第7198期|1072-1078qt0003|共8页
  • 作者单位

    Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology,Harvard Medical School, New Research Building, 330 Brookline Avenue, Boston, Massachusetts 02215, USA Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10021, USA Department of Pathology, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10021, USA;

    Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology,Harvard Medical School, New Research Building, 330 Brookline Avenue, Boston, Massachusetts 02215, USA Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10021, USA Department of Pathology, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10021, USA;

    Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology,Harvard Medical School, New Research Building, 330 Brookline Avenue, Boston, Massachusetts 02215, USA Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10021, USA Department of Pathology, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10021, USA;

    Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan;

    Division of Hematology and Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, Turin 10043, Italy;

    Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan;

    Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, New Research Building, 330 Brookline Avenue, Boston, Massachusetts 02215, USA;

    Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, New Research Building, 330 Brookline Avenue, Boston, Massachusetts 02215, USA;

    Department of Pathology, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10021, USA;

    Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology,Harvard Medical School, New Research Building, 330 Brookline Avenue, Boston, Massachusetts 02215, USA Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10021, USA Department of Pathology, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10021, USA;

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  • 正文语种 eng
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